pH-Sensitive nanoparticles containing 5-fluorouracil and leucovorin as an improved anti-cancer option for colon cancer

Parenteral administration of chemotherapeutic drugs, 5-fluorouracil (5-FU) and leucovorin (LV), is commonly used to treat large bowel carcinomas such as colon cancer (CC) and colorectal carcinoma (CRC). Our study aims to design a novel nanoparticulate drug-delivery vehicle for oral use capable of colon-specific release. A modified double-emulsion solvent evaporation method was used in the preparation of pH-responsive Eudargit S100 polymeric nanoparticles, loaded with 5-FU/LV combination (5-FU/LV-loaded Eudargit S100 NPs). Our optimized drug-loaded NP showed a pH-responsive drug release and exhibited significantly more cytotoxic actions in cancer-cell lines than free drugs. These findings open the way for conducting clinical trials for colon malignancies treated with nanoparticles

Predictor factors of sustained virological response in patients with chronic hepatitis C treated with current direct-acting antiviral drugs

Purpose: To assess the efficacy and predictors of treatment response of chronic hepatitis C genotype 4 Egyptian patients with sofosbuvir and daclatasvir, with or without ribavirin.Methods: This prospective study enrolled 200 patients with chronic hepatitis C virus (HCV) genotype 4 infection who received sofosbuvir plus daclatasvir for 12 weeks, with the addition of ribavirin for treating cirrhotic patients. Immunological parameters such as natural killer (NK) cell percentage, phenotype, and serum C-X-C motif chemokine 10 (CXCL10) were evaluated prior to treatment and at the end of the treatment.Results: Overall, 92.5 % of the patients achieved sustained virological response at 12 weeks (SVR12), where the non-cirrhotic group had 96.29 % SVR12, while the cirrhotic group had 84.61 % SVR12. Nonresponders had lower pretreatment platelet count, higher CXCL10 levels, and lower baseline frequencies of NK cells and NK subgroup CD56- CD16+.Conclusion: Based on these results, the use of sofosbuvir plus daclatasvir with or without ribavirin for 12 weeks, is an effective regimen in the treatment of Egyptian patients infected with genotype 4 HCV. The predictors of non-response are advanced age, liver cirrhosis, lower pretreatment platelet count, higher level of CXCL10, lower baseline NK cells frequency and percentage of the dysfunctional subset CD56- CD16+. Keywords: Hepatitis C virus, Genotype 4, Sofosbuvir, Daclatasvir, Sustained virological respons

Toll-like Receptor 3 Regulates Neural Stem Cell Proliferation by Modulating the Sonic Hedgehog Pathway

Toll-like receptor 3 (TLR3) signaling has been implicated in neural stem/precursor cell (NPC) proliferation. However, the molecular mechanisms involved, and their relationship to classical TLR-mediated innate immune pathways, remain unknown. Here, we report investigation of the mechanics of TLR3 signaling in neurospheres comprised of epidermal growth factor (EGF)-responsive NPC isolated from murine embryonic cerebral cortex of C57BL/6 (WT) or TLR3 deficient (TLR3−/−) mice. Our data indicate that the TLR3 ligand polyinosinic-polycytidylic acid (PIC) negatively regulates NPC proliferation by inhibiting Sonic Hedgehog (Shh) signaling, that PIC induces apoptosis in association with inhibition of Ras-ERK signaling and elevated expression of Fas, and that these effects are TLR3-dependent, suggesting convergent signaling between the Shh and TLR3 pathways

Design, synthesis and antitumor evaluation of novel pyrazolopyrimidines and pyrazoloquinazolines

A series of N-aryl-7-aryl-pyrazolo[1,5-a]pyrimidines 18a–u and N-aryl-pyrazolo[1,5-a] quinazolines 25a–c were designed and synthesized via the reaction of 5-aminopyrazoles 11a–c with enaminones 12a–g or 19, respectively. The new compounds were screened for their in vitro antitumor activity toward liver (HepG-2) and breast (MCF-7) human cancer cells using 3-[4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide MTT assay. From the results, it was found that all compounds showed dose-dependent cytotoxic activities against both HepG-2 and MCF-7 cells. Two compounds 18o and 18a were selected for further investigations. Cell cycle analysis of liver (HepG-2) cells treated with 18o and breast (MCF-7) cells treated with 18a showed cell cycle arrest at G2/M phase and pro-apoptotic activity as indicated by annexin V-FITC staining.publishedVersio

New Algorithm for Drawings of 3-Planar Graphs

Graphs arise in a natural way in many applications, together with the need to be drawn. Except for very small instances, drawing a graph by hand becomes a very complex task, which must be performed by automatic tools. The field of graph drawing is concerned with finding algorithms to draw graph in an aesthetically pleasant way, based upon a certain number of aesthetic criteria that define what a good drawing, (synonyms: diagrams, pictures, layouts), of a graph should be. This problem can be found in many such as in the computer networks, data networks, class inter-relationship diagrams in object oriented databases and object oriented programs, visual programming interfaces, database design systems, software engineering…etc. Given a plane graph G, we wish to find a drawing of G in the plane such that the vertices of G are represented as grid points, and the edges are represented as straight-line segments between their endpoints without any edge-intersection. Such drawings are called planar straight-line drawings of G. An additional objective is to minimize the area of the rectangular grid in which G is drawn. In this paper we introduce a new algorithms that finds an embedding of 3-planar graph. Keywords: 3- Planar Graph; Graph Drawing; drawing on grid

Amenability of heap leaching technology on uranium extraction from Gattar and El Missikat area, Eastern Desert, Egypt: A kinetic approach

Studies of uranium heap leaching from different uranium mineralization situated in Eastern Desert of Egypt was investigated via batch experiments, followed by its optimum condition applicationon column percolationtests.The optimum process operating parameters were implemented on large column scale in order to make more condition control and evaluate the time and reagents needed in the large scale. The results show thatleaching efficiency of GIIattained about 78.3% with 34kg/ton acid consumption in a 44 days period, while leaching efficiency of El-Missikat attained about 86.6% with 28kg/ton acid consumption in a 40 days period.Kinetics reaction models of column tests have been investigated to optimize the column leaching behavior. Based on the leaching results of two mineralized samples, the rate of the uranium metal dissolution is controlled by the chemical reaction and the diffusion reaction but diffusion reaction control was more predominate than a chemical reaction control

Kemijski sastav sojeva plijesni Monascus ruber

Chemical profile of Monascus ruber strains has been studied using gas chromatography-mass spectrometry (GC/MS) analysis. The colour intensity of the red pigment and secondary metabolic products of two M. ruber strains (AUMC 4066 and AUMC 5705) cultivated on ten different media were also studied. Metabolic products can be classified into four categories: anticholesterol, anticancer, food colouring, and essential fatty acids necessary for human health. Using GC/MS, the following 88 metabolic products were detected: butyric acid and its derivatives (25 products), other fatty acids and their derivatives (19 products), pyran and its derivatives (22 products) and other metabolites (22 products). Among these, 32 metabolites were specific for AUMC 4066 strain and 34 for AUMC 5705 strain, whereas 22 metabolites were produced by both strains on different tested substrates. Production of some metabolites depended on the substrate used. High number of metabolites was recorded in the red pigment extract obtained by both strains grown on malt broth and malt agar. Also, 42 aroma compounds were recorded (4 alcohols, 2 benzaldehydes, 27 esters, 3 lactones, 1 phenol, 1 terpenoid, 3 thiol compounds and acetate-3-mercapto butyric acid). Thin layer chromatography and GC/MS analyses revealed no mycotoxin citrinin in any media used for the growth of the two M. ruber strains.Svrha je rada bila proučiti kemijski sastav sojeva plijesni Monascus ruber pomoću plinske kromatografije i masene spektrometrije. Ispitan je i intenzitet crvenog pigmenta te sekundarni produkti metabolizma dvaju sojeva plijesni M. ruber (AUMC 4066 i AUMC 5705) uzgojenih na deset različitih podloga. Produkti metabolizma mogu se razvrstati u 4 skupine: spojevi koji snižavaju razinu kolesterola, antikancerogeni spojevi, prehrambene boje i esencijalne masne kiseline neophodne za ljudsko zdravlje. Plinskom je kromatografijom i masenom spektrometrijom pronađeno 88 produkata metabolizma, a među njima maslačna kiselina i njezini derivati (25), ostale masne kiseline i njihovi derivati (19), piran i njegovi derivati (22), te ostali metaboliti (22). Od ukupnog broja produkata, njih 33 je specifično za soj AUMC 4066, a 34 za soj AUMC 5705, dok su oba soja proizvela 22 produkta na različitim podlogama. Proizvodnja je produkata ovisila o upotrijebljenoj podlozi. Velik je broj metabolita pronađen u ekstraktima crvenog pigmenta iz oba soja uzgojena na podlogama od slada. Pronađena su 42 aromatska spoja, i to 4 alkohola, 27 estera, 3 laktona, 1 fenol, 1 terpenoid, 3 tiola i 1 merkapto spoj. Tankoslojnom i plinskom kromatografijom te masenom spektrometrijom nije pronađen mikotoksin citrinin ni u jednoj podlozi na kojoj su rasla ova dva soja plijesni M. ruber

Green Synthesis, Characterization, Antimicrobial and Anticancer Screening of New Metal Complexes Incorporating Schiff Base

A Schiff base ligand of o-vanillin and 4-aminoazobenzene and its transition metal complexes of Ni(II), Co(II), Zn(II), Cu(II), Mn(II), and Zr(IV) were prepared under microwave irradiation as a green approach compared to the conventional method. The structures of new compounds have been characterized and elucidated via elemental and spectroscopic analyses. In addition, magnetic susceptibility, electron spin resonance, and electronic spectra of the synthesized complexes explained their geometrical structures. The thermal stability of Cu(II), Zn(II), and Zr(IV) complexes was studied by thermo-gravimetric analyses (TGA). Coats–Redfern and Horowitz–Metzger equations were used to calculate the thermal and dehydration decomposition activities of proposed structures kinetically. Surface morphologies of the solid compounds were imaged by scanning electron microscopy (SEM). The particle size of prepared complexes was measured by using a particle size analyzer at a diffraction angle of 10.9°. The geometry structures of the synthesized compounds were verified utilizing electronic spectra, ESR spectrum, and magnetic moment value. The newly synthesized compounds were screened for antimicrobial activity. Also, the anticancer activity of the free Schiff base ligand and its metal complexes were studied against two cell lines: human colon (HCT-116) and human liver cancer cells (HepG-2). The obtained results showed that the Cu(II) complex displayed the highest cytotoxic activity (IC50 = 18 and 22 μg/mL for HepG-2 and HCT, respectively) compared to the free Schiff base ligand.publishedVersio

Feeding deterrence and larvicidal effects of latex serum and latex-synthesized nanoparticles of Calotropis procera against the cotton leafworm, Spodoptera littoralis

Background: Spodoptera littoralis is an important agricultural pest; thus, knowledge about the effect of latex serum and latex-synthesized nanoparticles of Calotropis procera on this species can assist in its management.. Nanotechnology is currently taking root in the agriculture economy as a substitute for pest management that is targeted, safe, and effective. The repellent and antifeedant efficacy of C. procera latex serum and its nanoparticles against S. littoralis fourth instar larvae was investigated in this work.Methods: The process of synthesizing silver nanoparticles has been carried out, followed by their subsequent characterization. The objective of this study was to assess the antifeedant properties of the latex serum and its nanoparticles against the 4th instar larvae of S. littoralis through the implementation of a bioassay.Results: With rising latex serum content, the proportion of repellency and hunger rose. In comparison to insects injected with latex serum, utilizing nanoparticles of LAgNPs with this larva via injection resulted in much increased mortality.Conclusion: According to the findings of this study, insects injected with LAgNPs died at a substantially higher rate than insects injected with latex serum. LAgNPs was efficient against S. littoralis larvae and can thus be utilized to specifically control the pest